Year: 2024
Type: article
Abstract: Use of one addictive drug typically influences the behavioral response to other drugs, either administered at the same time or a subsequent time point. The nature of the drugs being used, as well as the timing and dosing, also influence how these drugs interact. Here, we tested the effects of adolescent THC exposure on the development of morphine-induced behavioral adaptations following repeated morphine exposure during adulthood. We found that adolescent THC administration paradoxically prevented the development of anxiety-related behaviors that emerge during a forced abstinence period following morphine administration but facilitated reinstatement of morphine CPP. Following forced abstinence, we then mapped the whole-brain response to a moderate dose of morphine and found that adolescent THC administration led to an overall increase in brain-wide neuronal activity and increased the functional connectivity between frontal cortical regions and the ventral tegmental area. Last, we show using rabies virus-based circuit mapping that adolescent THC exposure triggers a long-lasting elevation in connectivity from the frontal cortex regions onto ventral tegmental dopamine cells. Our study adds to the rich literature on the interaction between drugs, including THC and opioids, and provides potential neural substates by which adolescent THC exposure influences responses to morphine later in life.
Source: Neuropsychopharmacology
Institution: University of California, Irvine
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Funders: National Science Foundation, U.S. Department of Health and Human Services, Tobacco-Related Disease Research Program, BrightFocus Foundation, National Alliance for Research on Schizophrenia and Depression, One Mind, National Institutes of Health, University of California, Irvine, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: G1178403614, G1213143777, G1864335048, G2136068807, On circuit mechanisms of reward behaviors after early-life adversity, G3034545754, Identifying circuit drivers of early AD pathogenesis, G4029146187, G4309869417, G4988360362, Ventral Pallidum Circuits Underlying Preclinical Models of Opioid Addiction, G535910574, G5848453910, G5869998495, G5957618476, Investigation of neural ensembles driving pain chronification, G7103400781, Graduate Research Fellowship (GRFP), G8843225178, G9000000562, G9000070663, G9000091225, G9000147689, G9000167467, G9000179012, G9000220978, Circuitry dynamics underlying opioid-dependence: Integrating structural, functional, and transcriptomic mechanisms, On circuit mechanisms of reward behaviors after early-life adversity, Dynamic epigenomic landscape of opioid abuse following early-life adversity
OpenAlex ID: W4405222800